Myofiber androgen receptor increases muscle strength mediated by a skeletal muscle splicing variant of Mylk4

Autor: Iori Sakakibara, Yuta Yanagihara, Koichi Himori, Takashi Yamada, Hiroshi Sakai, Yuichiro Sawada, Hirotaka Takahashi, Noritaka Saeki, Hiroyuki Hirakawa, Atsushi Yokoyama, So-ichiro Fukada, Tatsuya Sawasaki, Yuuki Imai
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: iScience, Vol 24, Iss 4, Pp 102303- (2021)
Druh dokumentu: article
ISSN: 2589-0042
DOI: 10.1016/j.isci.2021.102303
Popis: Summary: Androgens have a robust effect on skeletal muscles to increase muscle mass and strength. The molecular mechanism of androgen/androgen receptor (AR) action on muscle strength is still not well known, especially for the regulation of sarcomeric genes. In this study, we generated androgen-induced hypertrophic model mice, myofiber-specific androgen receptor knockout (cARKO) mice supplemented with dihydrotestosterone (DHT). DHT treatment increased grip strength in control mice but not in cARKO mice. Transcriptome analysis by RNA-seq, using skeletal muscles obtained from control and cARKO mice treated with or without DHT, identified a fast-type muscle-specific novel splicing variant of Myosin light-chain kinase 4 (Mylk4) as a target of AR in skeletal muscles. Mylk4 knockout mice exhibited decreased maximum isometric torque of plantar flexion and passive stiffness of myofibers due to reduced phosphorylation of Myomesin 1 protein. This study suggests that androgen-induced skeletal muscle strength is mediated with Mylk4 and Myomesin 1 axis.
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